MOLECULAR SCREENING SHARED RESOURCE (MSSR) ABSTRACT The goal of the UCLA Jonsson Comprehensive Cancer Center (JCCC) Molecular Screening Shared Resource (MSSR) is to provide transformative high throughput screening (HTS) capabilities to the UCLA research community and beyond. The MSSR offers a comprehensive array of HTS services enabling JCCC investigators to discover new molecular targets, identify small molecule drugs for these targets, and characterize and optimize candidate agents in preparation for clinical assessments. Established in 2003, the MSSR has grown from 2,085 sf. in 2013 to 3,600 sf. of BSL2+ compatible space in 2017. The cumulative number of faculty users nearly tripled from 86 to 237 users in the prior project period. During the last six years, the cumulative amount of extramural cancer relevant funding brought to UCLA by leveraging MSSR capabilities reached ~$180M. Since 2013, 20 JCCC members used the MSSR, representing 70% of overall usage, with 40% from members with peer-reviewed funding. MSSR collaborations contributed to 68 cancer-relevant publications from 2013 ? 2018 with 43% of these in high impact (IF ?10, or field leading) journals. A comprehensive set of services cover assay development, HTS, data analysis, and follow-up work, such as potency and toxicity determinations and selectivity testing. The MSSR offers access to 200,000 compounds in various libraries for chemical genomics, repurposing, and drug discovery. The MSSR also offers a wide array of functional genomics libraries, including human genome-wide arrayed CRISPR and shRNA lentiviral constructs, siRNAs covering the mouse and human druggable genomes, and genome-wide cDNA libraries in lentiviral and transfection ready formats. Projects are research partnerships between MSSR staff and JCCC faculty members, supported by three expert MSSR scientists on four fully automated, robotic screening systems, with a per diem capacity exceeding 100K samples in 384 well plate format. All plate reader based assays and plate formats are addressable, as are advanced assay readouts, such as phenotypic screening by confocal spinning disk microscopy. The MSSR follows a collaborative model that integrates the user into a project team consisting of a JCCC investigator, MSSR leadership, and MSSR scientists. The integration of the users into the project team also brings the necessary biological knowledge to the project while keeping the MSSR headcount and associated cost low but scalable with demand. Moreover, this is an excellent educational opportunity for students to learn in one-on-one training from MSSR experts. All projects utilize best industry practices including the generation of SOPs and milestone driven project management. MSSR Director Robert Damoiseaux, PhD (ZY) is an internationally known expert in HTS with an industry background who frequently provides talks at national meetings and guides each project in the MSSR, ensuring research excellence. The year 2017 was pivotal for the MSSR, with the first drug based on a molecule discovered at the MSSR entering clinical trials for myelodysplastic syndrome and acute myeloid leukemia.